Depression, Heart Disease and Platelets: Connecting the Dots

Date: June 15, 2012

Building on Roy Ziegelstein’s research, Marlene Williams is studying platelet activation in patients with cardiovascular disease and depression.

photo by Keith Weller

Every day, Marlene Williams sees heart attack patients in the cardiac intensive care unit who are in a dark mood. The Johns Hopkins Bayview cardiologist and CCU director is still surprised at how depressed they seem, and her concern runs deep: “I worry that they won’t take their meds and follow up.”

We have long known that men and women with heart disease and depression are at higher risk for heart attacks and mortality, she says. But how do we understand the biological mechanisms behind this link? Could platelets have a role?

Williams is working alongside cardiologist Roy Ziegelstein, who studies connections between depression and heart disease, to find out. Drawing from her experience as a platelet researcher, Williams is spearheading an NIH-funded study to test for a hypothesized mechanistic tie between depression and platelet function, assessed by various measures of platelet activation.

Ziegelstein has long bemoaned the “big gap in understanding” about the role of platelets in patients with heart disease and depression. Platelets are rich in serotonin, a major neurotransmitter in the central nervous system. Most of the body’s serotonin resides in platelets.

But to date, says Ziegelstein, there are very few high-quality platelet studies in depressed patients; the smaller ones differ dramatically in their methods and results. “The large differences in methods and inconsistent findings make a meta-analysis virtually impossible,” Ziegelstein says. “With this study, Marlene is breaking new ground.”

What sets her work apart, says Ziegelstein, is that she’s evaluating patients with heart disease rather than depressed patients who are otherwise healthy. She’s also processing the blood immediately after it’s drawn, then using uniform, accepted methods to stimulate platelets in the lab to assess their activation.

Since the platelet study opened last winter, 60 of a planned 300 patients have been enrolled. Already, Williams’ findings show a trend toward positive correlation between serotonin platelet aggregation and higher Beck Depression Inventory scores, a standard measure of a person’s symptoms of depression.

Ziegelstein is convinced that feelings of sadness can alter a person’s biological makeup. And an earlier study of his with common antidepressants—selective serotonin reuptake inhibitors (SSRI)—showed that heart disease patients who received SSRIs had slightly better cardiac outcomes than patients not receiving these medications. Besides improving mood, antidepressants may have the added benefit of breaking up “sticky” platelets common in cardiac patients, which can trigger heart attacks.

Regardless of the outcome of Williams’ study, he says, a patient’s emotional state should never be discounted in clinical practice. “It’s very easy for cardiologists to focus on heart health and to overlook the patient’s mental health,” says Ziegelstein.

At the very least, he adds, diagnosing and successfully treating depression in patients with heart disease could enhance quality of life and may even improve compliance with drug therapy. And, “if we understand what’s happening mechanistically, we can provide better treatments for these patients.”